tbuckley/cabot-search huggingface dataset:
ABCA3-related interstitial lung disease beyond infancy
Authors: Yang Li, Elias Seidl, Katrin Knoflach, Florian Gothe, Maria Elisabeth Forstner, Katarzyna Michel, Ingo Pawlita, Florian Gesenhues, Franziska Sattler, Xiaohua Yang, Carolin Kroener, Simone Reu-Hofer, Julia Ley-Zaporozhan, Birgit Kammer, Ingrid Krüger-Stollfuß, Julien Dinkel, Julia Carlens, Martin Wetzke, Antonio Moreno-Galdó, Alba Torrent-Vernetta, Joanna Lange, Katarzyna Krenke, Nisreen Rumman, Sarah Mayell, Tugba Sismanlar, Ayse Aslan, Nicolas Regamey, Marijke Proesmans, Florian Stehling, Lutz Naehrlich, Kilinc Ayse, Sebastian Becker, Cordula Koerner-Rettberg, Erika Plattner, Effrosyni D Manali, Spyridon A Papiris, Ilaria Campo, Matthias Kappler, Nicolaus Schwerk, Matthias Griese
Journal: Thorax (2023)

Background The majority of patients with childhood interstitial lung disease (chILD) caused by pathogenic variants in ATP binding cassette subfamily A member 3 (ABCA3) develop severe respiratory insufficiency within their first year of life and succumb to disease if not lung transplanted. This register-based cohort study reviews patients with ABCA3 lung disease who survived beyond the age of 1 year. Method Over a 21-year period, patients diagnosed as chILD due to ABCA3 deficiency were identified from the Kids Lung Register database. 44 patients survived beyond the first year of life and their long-term clinical course, oxygen supplementation and pulmonary function were reviewed. Chest CT and histopathology were scored blindly. Results At the end of the observation period, median age was 6.3 years (IQR: 2.8–11.7) and 36/44 (82%) were still alive without transplantation. Patients who had never received supplemental oxygen therapy survived longer than those persistently required oxygen supplementation (9.7 (95% CI 6.7 to 27.7) vs 3.0 years (95% CI 1.5 to 5.0), p = 0.0126). Interstitial lung disease was clearly progressive over time based on lung function (forced vital capacity % predicted absolute loss −1.1% /year) and on chest CT (increasing cystic lesions in those with repetitive imaging). Lung histology pattern were variable (chronic pneumonitis of infancy, non-specific interstitial pneumonia, and desquamative interstitial pneumonia). In 37/44 subjects, the ABCA3 sequence variants were missense variants, small insertions or deletions with in-silico tools predicting some residual ABCA3 transporter function. Conclusion The natural history of ABCA3-related interstitial lung disease progresses during childhood and adolescence. Disease-modifying treatments are desirable to delay such disease course.
Tracheostomy in children is associated with neutrophilic airway inflammation
Authors: Jason Powell, Steven Powell, Michael W Mather, Lauren Beck, Andrew Nelson, Pawel Palmowski, Andrew Porter, Jonathan Coxhead, Ann Hedley, Jonathan Scott, Anthony J Rostron, Thomas P Hellyer, Fatima Zaidi, Tracey Davey, James P Garnett, Rachel Agbeko, Chris Ward, Christopher J Stewart, Clifford C Taggart, Malcolm Brodlie, A John Simpson
Journal: Thorax (2023)

Background Tracheostomies in children are associated with significant morbidity, poor quality of life, excess healthcare costs and excess mortality. The underlying mechanisms facilitating adverse respiratory outcomes in tracheostomised children are poorly understood. We aimed to characterise airway host defence in tracheostomised children using serial molecular analyses. Methods Tracheal aspirates, tracheal cytology brushings and nasal swabs were prospectively collected from children with a tracheostomy and controls. Transcriptomic, proteomic and metabolomic methods were applied to characterise the impact of tracheostomy on host immune response and the airway microbiome. Results Children followed up serially from the time of tracheostomy up to 3 months postprocedure (n=9) were studied. A further cohort of children with a long-term tracheostomy were also enrolled (n=24). Controls (n=13) comprised children without a tracheostomy undergoing bronchoscopy. Long-term tracheostomy was associated with airway neutrophilic inflammation, superoxide production and evidence of proteolysis when compared with controls. Reduced airway microbial diversity was established pre-tracheostomy and sustained thereafter. Conclusions Long-term childhood tracheostomy is associated with a inflammatory tracheal phenotype characterised by neutrophilic inflammation and the ongoing presence of potential respiratory pathogens. These findings suggest neutrophil recruitment and activation as potential exploratory targets in seeking to prevent recurrent airway complications in this vulnerable group of patients.
Topological data analysis identifies molecular phenotypes of idiopathic pulmonary fibrosis
Authors: Andrew Shapanis, Mark G Jones, James Schofield, Paul Skipp
Journal: Thorax (2023)

Background Idiopathic pulmonary fibrosis (IPF) is a debilitating, progressive disease with a median survival time of 3–5 years. Diagnosis remains challenging and disease progression varies greatly, suggesting the possibility of distinct subphenotypes. Methods and results We analysed publicly available peripheral blood mononuclear cell expression datasets for 219 IPF, 411 asthma, 362 tuberculosis, 151 healthy, 92 HIV and 83 other disease samples, totalling 1318 patients. We integrated the datasets and split them into train (n=871) and test (n=477) cohorts to investigate the utility of a machine learning model (support vector machine) for predicting IPF. A panel of 44 genes predicted IPF in a background of healthy, tuberculosis, HIV and asthma with an area under the curve of 0.9464, corresponding to a sensitivity of 0.865 and a specificity of 0.89. We then applied topological data analysis to investigate the possibility of subphenotypes within IPF. We identified five molecular subphenotypes of IPF, one of which corresponded to a phenotype enriched for death/transplant. The subphenotypes were molecularly characterised using bioinformatic and pathway analysis tools identifying distinct subphenotype features including one which suggests an extrapulmonary or systemic fibrotic disease. Conclusions Integration of multiple datasets, from the same tissue, enabled the development of a model to accurately predict IPF using a panel of 44 genes. Furthermore, topological data analysis identified distinct subphenotypes of patients with IPF which were defined by differences in molecular pathobiology and clinical characteristics.
Are Senolytic Agents Guilty of Overkill or Inappropriate Age Discrimination?
Authors: Marlene Rabinovitch
Journal: Circulation (2023)

n this issue of Circulation, Born et al, 1 from Dr Serge Adnot's group, show that agents that induce senescence in cells of the pulmonary vasculature can unexpectedly worsen rather than ameliorate pulmonary hypertension (PH).The study has particularly important translational implications because it indicates that the potential efficacy of an emerging therapy relies on the underlying disease mechanism and animal model used, cell specificity, dose, and route of administration.The authors began by showing that in human lung tissue from patients with PH, ≈30% of lung endothelial cells (ECs) and smooth muscle cells (SMCs) have elevated P16, an observation recently reported by others. 2 As further evidence of senescence, many of the cells with elevated P16 also had an increase in unrepaired DNA damage marked by γH2AX and 53BP1.The authors used multiple senolytic strategies in several animal models to remove senescent cells and found unexpectedly that eliminating senescent cells aggravated rather than suppressed PH development.The authors examined a number of animal models of PH, including rats exposed to chronic hypoxia, rats injected with the toxin monocrotaline, rats injected with the vascular endothelial growth factor receptor blocker Sugen 5416 before exposure to chronic hypoxia, mice overexpressing the serotonin transporter in SMCs (SM22-HTT [smooth muscle protein 22-HT transporter]), and mice with P16 overexpression that develop PH with age.These animals received the senolytic ABT-263 or FOXO4-DRI (forkhead box O transcription factor 4-D-retro-inverso) that would be expected to remove senolytic ECs or SMCs, with equivalent results.
Shortening Tuberculosis Treatment — A Strategic Retreat
Authors: Véronique Dartois, Eric J. Rubin
Journal: New England Journal of Medicine (2023)

Our current treatment regimen for tuberculosis, which goes by the somewhat ironic name of "directly observed therapy, short course," is anything but short. Patients are treated, generally on a daily basis, for 6 months, which necessitates an infrastructure to deliver and observe therapy. This logistic burden has led to a push for shorter treatments. Although many initial attempts failed, a recent study suggested that a newer regimen could lead to a similar probability of cure in 4 months.1 This is certainly an advantage, and yet the newer regimen, if widely used, would still require a similarly burdensome infrastructure. Can we . . .
Longitudinal Echocardiogram Imaging in the First Genetically Modified Porcine to Human Cardiac Xenotransplant
Authors: Susie N. Hong, Muhammad M. Mohiuddin, Manjula Ananthram, Cullen Soares, Corbin E. Goerlich, Timm L. Dickfeld, Peter Hanna, Charles C. Hong, Michael Benitez, Susan M. Joseph, Anuj Gupta, Alison Grazioli, Bartley P. Griffith
Journal: JACC. Cardiovascular imaging (2023)
Towards clinical breakpoints for non-tuberculous mycobacteria – Determination of epidemiological cut off values for the Mycobacterium avium complex and Mycobacterium abscessus using broth microdilution
Authors: Gabrielle Fröberg, Florian P. Maurer, Erja Chryssanthou, Louise Fernström, Hanaa Benmansour, Samira Boarbi, Anne Torunn Mengshoel, Peter Michael Keller, Miguel Viveiros, Diana Machado, Margaret M. Fitzgibbon, Simone Mok, Jim Werngren, Daniela Maria Cirillo, Fernando Alcaide, Hanne-Leena Hyyryläinen, Alexandra Aubry, Sönke Andres, Darshaalini Nadarajan, Erik Svensson, John Turnidge, Christian G. Giske, Gunnar Kahlmeter, Emmanuelle Cambau, Jakko van Ingen, Thomas Schön
Journal: Clinical Microbiology and Infection (2023)

For non-tuberculous mycobacteria (NTM), minimum inhibitory concentration (MIC) distributions of wild-type isolates have not been systematically evaluated despite their importance for establishing antimicrobial susceptibility testing (AST) breakpoints. We gathered MIC distributions for drugs used against the Mycobacterium avium complex (MAC) and Mycobacterium abscessus (MAB) obtained by commercial broth microdilution (SLOMYCOI and RAPMYCOI) from 12 laboratories. Epidemiological cut-off values (ECOFFs) and tentative ECOFFs (TECOFFs) were determined by EUCAST methodology including quality control (QC) strains. The clarithromycin ECOFF was 16 mg/L for M. avium (n = 1271) whereas TECOFFs were 8 mg/L for M. intracellulare (n = 415) and 1 mg/L for MAB (n = 1014) confirmed by analysing MAB subspecies without inducible macrolide resistance (n = 235). For amikacin, the ECOFFs were 64 mg/L for MAC and MAB. For moxifloxacin, the WT spanned >8 mg/L for both MAC and MAB. For linezolid, the ECOFF and TECOFF were 64 mg/L for M. avium and M. intracellulare, respectively. Current CLSI breakpoints for amikacin (16 mg/L), moxifloxacin (1 mg/L) and linezolid (8 mg/L) divided the corresponding WT distributions. For QC M. avium and M. peregrinum, ≥95% of MIC values were well within recommended QC ranges. As a first step towards clinical breakpoints for NTM, (T)ECOFFs were defined for several antimicrobials against MAC and MAB. Broad wild-type MIC distributions indicate a need for further method refinement which is now under development within the EUCAST subcommittee for anti-mycobacterial drug susceptibility testing. In addition, we showed that several CLSI NTM breakpoints are not consistent in relation to the (T)ECOFFs.
Outcomes of Simultaneous Heart and Kidney Transplantation
Authors: Shinobu Itagaki, Nana Toyoda, Noah Moss, Donna Mancini, Natalia Egorova, Takahisa Mikami, Erick Sun, Yuki Bekki, Gregory Serrao, Anuradha Lala, Percy Boateng, David H. Adams, Anelechi C. Anyanwu
Journal: Journal of the American College of Cardiology (2023)
Sex Differences in Early Rhythm Control of Atrial Fibrillation in the EAST-AFNET 4 Trial
Authors: Isabelle C. Van Gelder, Neda Khalilian Ekrami, Katrin Borof, Thomas Fetsch, Christina Magnussen, Bart A. Mulder, Renate Schnabel, Karl Wegscheider, Michiel Rienstra, Paulus Kirchhof
Journal: Journal of the American College of Cardiology (2023)
Cardiac Damage and Quality of Life After Aortic Valve Replacement in the PARTNER Trials
Authors: Philippe Généreux, David J. Cohen, Philippe Pibarot, Björn Redfors, Jeroen J. Bax, Yanglu Zhao, Heather Prince, Raj R. Makkar, Samir Kapadia, Vinod H. Thourani, Michael J. Mack, Tamim M. Nazif, Brian R. Lindman, Vasilis Babaliaros, Mark Russo, James M. McCabe, Linda D. Gillam, Maria C. Alu, Rebecca T. Hahn, John G. Webb, Martin B. Leon, Suzanne V. Arnold
Journal: Journal of the American College of Cardiology (2023)
Face your fears: attenuating remote fear memories by reconsolidation-updating
Authors: Bianca A. Silva, Johannes Gräff
Journal: Trends in Cognitive Sciences (2023)

Traumatic events generate some of the most enduring memories, yet little is known about how long-lasting fear memories can be attenuated. In this review, we collect the surprisingly sparse evidence on remote fear memory attenuation from both animal and human research. What is becoming apparent is twofold: although remote fear memories are more resistant to change compared with recent ones, they can nevertheless be attenuated when interventions are targeted toward the period of memory malleability instigated by memory recall, the reconsolidation window. We describe the physiological mechanisms underlying remote reconsolidation-updating approaches and highlight how they can be enhanced through interventions promoting synaptic plasticity. By capitalizing on an intrinsically relevant phase of memory, reconsolidation-updating harbors the potential to permanently alter remote fear memories.
Short-Term Risk Stratification of Non–Flow-Limiting Coronary Stenosis by Angiographically Derived Radial Wall Strain
Authors: Shengxian Tu, Bo Xu, Lianglong Chen, Huihong Hong, Zhiqing Wang, Chunming Li, Miao Chu, Lei Song, Changdong Guan, Bo Yu, Zening Jin, Guosheng Fu, Xuebo Liu, Junqing Yang, Yundai Chen, Junbo Ge, Shubin Qiao, William Wijns
Journal: Journal of the American College of Cardiology (2023)
Early morning university classes are associated with impaired sleep and academic performance
Authors: Sing Chen Yeo, Clin K. Y. Lai, Jacinda Tan, Samantha Lim, Yuvan Chandramoghan, Teck Kiang Tan, Joshua J. Gooley
Journal: Nature Human Behaviour (2023)

Abstract Attending classes and sleeping well are important for students’ academic success. Here, we tested whether early morning classes are associated with lower attendance, shorter sleep and poorer academic achievement by analysing university students’ digital traces. Wi-Fi connection logs in 23,391 students revealed that lecture attendance was about ten percentage points lower for classes at 08:00 compared with later start times. Diurnal patterns of Learning Management System logins in 39,458 students and actigraphy data in 181 students demonstrated that nocturnal sleep was an hour shorter for early classes because students woke up earlier than usual. Analyses of grades in 33,818 students showed that the number of days per week they had morning classes was negatively correlated with grade point average. These findings suggest concerning associations between early morning classes and learning outcomes.
Genome assembly and genetic dissection of a prominent drought-resistant maize germplasm
Authors: Tian Tian, Shuhui Wang, Shiping Yang, Zhirui Yang, Shengxue Liu, Yijie Wang, Huajian Gao, Shuaisong Zhang, Xiaohong Yang, Caifu Jiang, Feng Qin
Journal: Nature Genetics (2023)
A meta-analysis of genetic effects associated with neurodevelopmental disorders and co-occurring conditions
Authors: Agnieszka Gidziela, Yasmin I. Ahmadzadeh, Giorgia Michelini, Andrea G. Allegrini, Jessica Agnew-Blais, Lok Yan Lau, Megan Duret, Francesca Procopio, Emily Daly, Angelica Ronald, Kaili Rimfeld, Margherita Malanchini
Journal: Nature Human Behaviour (2023)

Abstract A systematic understanding of the aetiology of neurodevelopmental disorders (NDDs) and their co-occurrence with other conditions during childhood and adolescence remains incomplete. In the current meta-analysis, we synthesized the literature on (1) the contribution of genetic and environmental factors to NDDs, (2) the genetic and environmental overlap between different NDDs, and (3) the co-occurrence between NDDs and disruptive, impulse control and conduct disorders (DICCs). Searches were conducted across three platforms: Web of Science, Ovid Medline and Ovid Embase. Studies were included only if 75% or more of the sample consisted of children and/or adolescents and the studies had measured the aetiology of NDDs and DICCs using single-generation family designs or genomic methods. Studies that had selected participants on the basis of unrelated diagnoses or injuries were excluded. We performed multilevel, random-effects meta-analyses on 296 independent studies, including over four million (partly overlapping) individuals. We further explored developmental trajectories and the moderating roles of gender, measurement, geography and ancestry. We found all NDDs to be substantially heritable (family-based heritability, 0.66 (s.e. = 0.03); SNP heritability, 0.19 (s.e. = 0.03)). Meta-analytic genetic correlations between NDDs were moderate (grand family-based genetic correlation, 0.36 (s.e. = 0.12); grand SNP-based genetic correlation, 0.39 (s.e. = 0.19)) but differed substantially between pairs of disorders. The genetic overlap between NDDs and DICCs was strong (grand family-based genetic correlation, 0.62 (s.e. = 0.20)). While our work provides evidence to inform and potentially guide clinical and educational diagnostic procedures and practice, it also highlights the imbalance in the research effort that has characterized developmental genetics research.
When to update COVID-19 vaccine composition
Authors: Rebecca Grant, Jilian A. Sacks, Priya Abraham, Supamit Chunsuttiwat, Cheryl Cohen, J. Peter Figueroa, Thomas Fleming, Paul Fine, David Goldblatt, Hideki Hasegawa, C. Raina MacIntrye, Ziad A. Memish, Elizabeth Miller, Sergio Nishioka, Amadou A. Sall, Samba Sow, Oyewale Tomori, Youchun Wang, Maria D. Van Kerkhove, Marie-Ange Wambo, Homa Attar Cohen, Samuel Mesfin, James R. Otieno, Lorenzo Subissi, Sylvie Briand, David E. Wentworth, Kanta Subbarao
Journal: Nature Medicine (2023)
A wearable platform for closed-loop stimulation and recording of single-neuron and local field potential activity in freely moving humans
Authors: Uros Topalovic, Sam Barclay, Chenkai Ling, Ahmed Alzuhair, Wenhao Yu, Vahagn Hokhikyan, Hariprasad Chandrakumar, Dejan Rozgic, Wenlong Jiang, Sina Basir-Kazeruni, Sabrina L. Maoz, Cory S. Inman, Matthias Stangl, Jay Gill, Ausaf Bari, Aria Fallah, Dawn Eliashiv, Nader Pouratian, Itzhak Fried, Nanthia Suthana, Dejan Markovic
Journal: Nature Neuroscience (2023)

Abstract Advances in technologies that can record and stimulate deep brain activity in humans have led to impactful discoveries within the field of neuroscience and contributed to the development of novel therapies for neurological and psychiatric disorders. Further progress, however, has been hindered by device limitations in that recording of single-neuron activity during freely moving behaviors in humans has not been possible. Additionally, implantable neurostimulation devices, currently approved for human use, have limited stimulation programmability and restricted full-duplex bidirectional capability. In this study, we developed a wearable bidirectional closed-loop neuromodulation system (Neuro-stack) and used it to record single-neuron and local field potential activity during stationary and ambulatory behavior in humans. Together with a highly flexible and customizable stimulation capability, the Neuro-stack provides an opportunity to investigate the neurophysiological basis of disease, develop improved responsive neuromodulation therapies, explore brain function during naturalistic behaviors in humans and, consequently, bridge decades of neuroscientific findings across species.
In-depth virological and immunological characterization of HIV-1 cure after CCR5Δ32/Δ32 allogeneic hematopoietic stem cell transplantation
Authors: Björn-Erik Ole Jensen, Elena Knops, Leon Cords, Nadine Lübke, Maria Salgado, Kathleen Busman-Sahay, Jacob D. Estes, Laura E. P. Huyveneers, Federico Perdomo-Celis, Melanie Wittner, Cristina Gálvez, Christiane Mummert, Caroline Passaes, Johanna M. Eberhard, Carsten Münk, Ilona Hauber, Joachim Hauber, Eva Heger, Jozefien De Clercq, Linos Vandekerckhove, Silke Bergmann, Gábor A. Dunay, Florian Klein, Dieter Häussinger, Johannes C. Fischer, Kathrin Nachtkamp, Joerg Timm, Rolf Kaiser, Thomas Harrer, Tom Luedde, Monique Nijhuis, Asier Sáez-Cirión, Julian Schulze zur Wiesch, Annemarie M. J. Wensing, Javier Martinez-Picado, Guido Kobbe
Journal: Nature Medicine (2023)

Abstract Despite scientific evidence originating from two patients published to date that CCR5Δ32/Δ32 hematopoietic stem cell transplantation (HSCT) can cure human immunodeficiency virus type 1 (HIV-1), the knowledge of immunological and virological correlates of cure is limited. Here we characterize a case of long-term HIV-1 remission of a 53-year-old male who was carefully monitored for more than 9 years after allogeneic CCR5Δ32/Δ32 HSCT performed for acute myeloid leukemia. Despite sporadic traces of HIV-1 DNA detected by droplet digital PCR and in situ hybridization assays in peripheral T cell subsets and tissue-derived samples, repeated ex vivo quantitative and in vivo outgrowth assays in humanized mice did not reveal replication-competent virus. Low levels of immune activation and waning HIV-1-specific humoral and cellular immune responses indicated a lack of ongoing antigen production. Four years after analytical treatment interruption, the absence of a viral rebound and the lack of immunological correlates of HIV-1 antigen persistence are strong evidence for HIV-1 cure after CCR5Δ32/Δ32 HSCT.